title: Environmental characteristics and oxidative stress of inhabitants and patients with amyotrophic lateral sclerosis in a high-incidence area on the Kii Peninsula, Japan.
abstract: OBJECTIVE
  Although Oshima, in the Kii Peninsula of Japan, is located within a high incidence area of amyotrophic lateral sclerosis (ALS) (Koza/Kozagawa/Kushimoto area, K area), no patients with ALS were detected between 1960 and 1999. However, the incidence recently increased between 2000 and 2009. On Oshima, the source of drinking water was changed from a regional river/wells to the Kozagawa River in the K area in 1975. We speculate that this change in water source may have played a role in the recent increase in the incidence of ALS. The aim of this study is to find contributing factors that may have triggered the locally high incidence of ALS.
  
  
  METHODS
  We investigated a possible association between the mineral content of drinking water and serum and oxidative stress markers among patients with ALS in the K area (K-ALS), residents of Oshima and controls.
  
  
  RESULTS
  We found that the levels of Ca and Zn in the recent drinking water in Oshima are low and that the serum levels of Ca and Zn in the Oshima residents and patients with K-ALS were significantly lower, while the oxidative stress markers were significantly higher, than those of the controls. The serum Zn and urinary 8-OHdG/creatinine levels explained 60% and 58% of the variations among the three groups, respectively. The serum Zn levels were negatively correlated with the serum Cu levels in the patients with K-ALS, and the serum Cu levels exhibited a tendency to be positively correlated with the 8-OHdG/creatinine levels in both the patients with K-ALS (r: 0.64) and the residents free from K-ALS (r: 0.32, p<0.01).
  
  
  CONCLUSIONS
  Taken together, we suggest that the low levels of Ca and Zn in the drinking water are possibly associated with an imbalance of metal metabolism in Oshima residents and an increase in oxidative stress markers in patients with K-ALS, although the causative relationship is not clear. This is a cross-sectional study, and a prospective study is needed in the future.
authors.affiliation: Department of Health Sciences, Kansai University of Health Sciences, Japan. tkihira815@kansai.ac.jp
authors.forename: Tameko
authors.initials: T
authors.lastname: Kihira
authors.forename: Kazushi
authors.initials: K
authors.lastname: Okamoto
authors.forename: Sohei
authors.initials: S
authors.lastname: Yoshida
authors.forename: Tetuya
authors.initials: T
authors.lastname: Kondo
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwai
authors.forename: Sachiko
authors.initials: S
authors.lastname: Wada
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kajimoto
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Kondo
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Kokubo
authors.forename: Shigeki
authors.initials: S
authors.lastname: Kuzuhara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D014877:Water Pollution, Chemical / Q000009:adverse effects*